Figure 1.

Unsaturated lipids can be acquired by desaturation of de novo synthesized fatty acids or by uptake of exogenous lipid. Saturated fatty acids have been shown to promote ER stress while unsaturated fatty acids counteract the effect of saturated lipid. The tumor microenvironment can contribute to ER stress by inhibiting optimal protein folding and SCD1 desaturase activity. Hypoxia can also increase lipid uptake, which counteracts the effects of SCD1 inhibition. Oncogenic signaling increases fatty acid synthesis and protein synthesis. Elevated rates of protein synthesis have been shown to increase ER stress. Oncogenic changes, such as activating Ras mutations, also promote lipid uptake.

SCD1: stearoyl-Coenzyme A desaturase 1

FAS: fatty acid synthase

ACC: acetyl-CoA carboxylase